1. Field of the Invention
The present disclosure relates to a nanopreparation having a micelle structure for diagnosis or treatment of cancer diseases, and a method of preparing the same, and more particularly, to a nanopreparation having a micelle structure available for diagnosis or treatment of cancer diseases, and a method of preparing the same, wherein the nanopreparation is prepared by encapsulating anti-cancer drug, such as a photosensitizer, by forming micelle with polymeric lipid DSPE-mPEG.
2. Description of the Related Art
Photodynamic therapy is one of currently promising method for treating cancers. Photodynamic therapy is a therapeutic method using a following principle: when a photosensitizer, which is a material sensitive to light, is administered to the body, singlet oxygen or free radicals are generated due to a chemical reaction which is induced by external light in the case where light having a particular wavelength is irradiated from the outside; and then, the singlet oxygen or free radicals induce apoptosis of various lesion sites or cancer cells to destroy them.
Photodynamic therapy is advantageous in that: only cancer cells can be selectively removed, while normal cells are retained. Due to the aforementioned advantages, photodynamic therapy has been studied in earnest from the 1980s, and clinical trials have been approved in Canada, Germany, and Japan in the 1990s. Thereafter, photodynamic therapy has been extensively used around the globe, for example, US FDA approved photodynamic therapy for esophagus cancer treatment in January 1996 and for early stage lung cancer treatment in September 1997.
Since a photosensitizer same as the photosensitizer used in photodynamic therapy can be frequently used even in photodynamic diagnosis, the photosensitizer is useful as a diagnostic and therapeutic agent of cancers. Photodynamic diagnosis has advantages in that: cancer diagnosis can be easily performed by using relatively simple equipment using optics without costly equipment such as computed tomography (CT) or magnetic resonance imaging for diagnosis of cancers; time consumption required to recognize the location or degree of cancers during an operation can be reduced; and real-time diagnosis can be performed as direct visual information is provided without an additional time for imaging. Accordingly, photodynamic diagnosis comes into the spotlight as a useful tool helping successful surgical removal of cancer. Usefulness of surgical removal using fluorescence of a photosensitizer was reported by W. Stummer, et al. in 2006 through clinical data (see Non-patent Documents 1). As such, active clinical application for diagnosis and surgical treatment of cancers has been made over regions ranging from Europe, as a starting point, to the US in 2000s in practice.
Glioblastoma holding 52% of a brain tumor is the most malignant tumor among the whole primary brain tumors. A five-year survival rate of glioblastoma is 5% or less. Glioblastoma is a fatal disease having an average survival time of 14 to 16 months even though aggressive and active treatment is performed. In the latest standard treatment of glioblastoma, concurrent chemoradiotherapy is performed after surgical removal. The standard treatment is based on the research result reported by the R. Stupp research team in 2005 in which the concurrent chemoradiotherapy using temozolomide prolongs an average survival time by 20.7% (see Non-patent Document 2). However, the therapeutic method has a problem in that the substantial average survival time can be prolonged by only 12.1 to 14.6 months. Accordingly, various therapeutic methods have been developed recently, followed by experimental and clinical attempts.
Various therapeutic methods for treating brain tumors have a problem in that a drug delivery system is less effective due to low drug permeability caused by a blood-brain barrier (BBB) and a blood tumor barrier (BTB) present in a brain; and a decrease in ability to deliver drug caused by an increase in pressure in tissue according to volumes and properties of brain tumors itself. However, an appearance of a drug delivery system using nanoparticles provides an epoch-making changeover in terms of drug delivery systems, wherein, the nanoparticles have advantages of prolonging a blood half-life, a reduction in toxicity to non-target organs, and significance of target organs or drug property modification according to feasibility of various surface modifications.
An effect of the drug delivery system using the nanoparticles is known to be decided by variables such as the size and physical properties of nanodrugs and an interrelationship between nanodrugs and brain tumor tissue or cells. Recently, the H. Sarin research team of National Institutes of Health in the US and the R. Jain research team of Harvard University have reported the research result that the size of the nanodrug used in brain tumors is suitably 12 nm or less to overcome a blood-tumor barrier (BTB) and interstitial fluid pressure in tissue (see Non-patent Documents 3 and 4). In consideration of the aforementioned research results, researches regarding adjustment of the size of the nanodrug are increasingly demanded in that the currently developed nanodrugs used to treat the brain tumor have the size of 20 nm or more.
Therefore, the present inventors have studied nanodrugs for photodynamic diagnosis or treatment, which may be used in brain tumors, resulting in the finding that a nanopreparation prepared by using hypericin as a photosensitizer and polymeric lipid DSPE-mPEG having a molecular weight of 1500 to 2500 has a size of 12 nm or less, light-induced cytotoxicity efficiency that is about more than 2.5 times higher than that of the case where only hypericin is used, and an improved relative coexistence coefficient to a mitochondrion among intracellular organelles of cancer, thereby completing the present invention.